Adrenal fast-track and enhanced recovery in retroperitoneoscopic surgery for primary aldosteronism improving patient outcome and efficiency.

PURPOSE: No data exist on perioperative strategies for enhancing recovery after posterior retroperitoneoscopic adrenalectomy (PRA). Our objective was to determine whether a multimodality adrenal fast-track and enhanced recovery (AFTER) protocol for PRA can reduce recovery time, improve patient satisfaction and maintain safety. METHODS: Thirty primary aldosteronism patients were included. Fifteen patients were treated with 'standard-of-care' PRA and compared with 15 in the AFTER protocol. The AFTER protocol contains: a preoperative information video, postoperative oral analgesics, early postoperative mobilisation and enteral feeding, and blood pressure monitoring at home. The primary outcome was recovery time. Secondary outcomes were length of hospital stay, postoperative pain and analgesics requirements, patient satisfaction, perioperative complications and quality of life (QoL). RESULTS: Recovery time was much shorter in both groups than anticipated and was not significantly different (median 28 days). Postoperative length of hospital stay was significantly reduced in AFTER patients (mean 32 vs 42 h, CI 95%, p = 0.004). No significant differences were seen in pain, but less analgesics were used in the AFTER group. Satisfaction improved amongst AFTER patients for time of admission and postoperative visit to the outpatient clinic. There were no significant differences in complication rates or QoL. CONCLUSION: Despite no difference in recovery time between the two groups, probably due to small sample size, the AFTER protocol led to shorter hospital stays and less analgesic use after surgery, whilst maintaining and even enhancing patient satisfaction for several aspects of perioperative care. Complication rates and QoL are comparable to standard-of-care.

Impact of Expanding Eligibility Criteria for Cochlear Implantation - Dynamic Modeling Study.

OBJECTIVES: Eligibility criteria for cochlear implantation (CI) are shifting due to technological and surgical improvements. The aim of this study was to explore the impact of further expanding unilateral CI criteria in those with severe hearing loss (HL) (61-80 dBHL) in terms of number of CI recipients, costs, quality of life, and cost-effectiveness. METHODS: A dynamic population-based Markov model was constructed mimicking the Dutch population in three age categories over a period of 20 years. Health states included severe HL (61-80 dBHL), profound HL (>81 dBHL), CI recipients, and no-CI recipients. Model parameters were based on published literature, (national) databases, expert opinion, and model calibration. RESULTS: If persons with severe HL would qualify and opt for CI similar to those with profound HL now, this would lead to a 6-7 times increase of new CI recipients and an associated increase in costs (€550 million) and QALYs (54.000) over a 20-year period (incremental cost utility ratio: 10.771 euros/QALY [2.5-97.5 percentiles: 1.252-23.171]). One-way-sensitivity analysis indicated that model outcomes were most sensitive to regaining employment, utility associated with having a CI, and costs of surgery and testing. CONCLUSION: Our findings suggest that expanding eligibility for CI to persons with severe HL could be a cost-effective use of resources. Clearly, however, it would require a significant increase in diagnostic, operative, and rehabilitative capacity. Our quantitative estimates can serve as a basis for a wider societal deliberation on the question whether such an increase can and should be pursued. LEVEL OF EVIDENCE: NA Laryngoscope, 133:924-932, 2023.

Challenges in Noninvasive Skin Biomarker Measurements in Daily Practice: A Longitudinal Study on Skin Surface Protein Detection by the Transdermal Analysis Patch in Pediatric Psoriasis.

INTRODUCTION: Skin surface proteins are potential biomarkers in psoriasis and can be measured noninvasively with the transdermal analysis patch (TAP). This study aimed to assess markers measured by TAP over time in daily clinical practice, explore their correlation with disease severity in pediatric psoriasis, and compare the TAP and tape stripping detection capability. METHODS: In this prospective observational daily clinical practice study, pediatric psoriasis patients (aged >5 to <18 years) were followed during 1 year. At each visit, TAPs were applied to lesional (n = 2), peri-lesional (n = 2), and non-lesional (n = 1) sites. Post-lesional skin was sampled if all lesions on the arms, legs, or trunk cleared. Treatment and psoriasis severity data were collected. IL-1RA, hBD-2, IL-1α, IL-8, VEGF, CXCL-1/2, CCL-27, IL-23, hBD-1, IL-22, IL-17A, KLK-5, and IL-4 levels were quantified by spot-ELISA. For the statistical analysis, Wilcoxon signed rank tests, Mann-Whitney U tests, and Spearman correlations were used. Detection capability of the TAP was compared to tape stripping in a separate cohort of adult psoriasis patients. RESULTS: 32 patients (median age 15.0 years, median Psoriasis Area and Severity Index [PASI] 5.2) were followed for a mean of 11.3 (±3.4) months with a total of 104 visits. In lesional skin (n = 197), significantly higher IL-1RA, hBD-2, IL-8, VEGF, CXCL-1/2, IL-23, hBD-1, IL-22, CCL-27, and IL-17A levels were found compared to non-lesional skin (n = 104), while IL-1α was higher in non-lesional skin. Marker levels were highly variable over time and did not correlate with disease severity measured by PASI or SUM scores. Comparison of the TAP and tape strip detection capability in adult psoriasis patients (n = 10) showed that lesional hBD-2, IL1-α, IL-8, and VEGF and non-lesional IL-1RA, hBD-2, IL-8, and VEGF were more frequently detected in tape extracts than TAPs. CONCLUSION: Due to the lack of correlation with clinical disease severity and the current detection capability of the markers measured by TAP in psoriasis, its use in regular practice is still a bridge too far.

CXCR4-directed [68Ga]Ga-PentixaFor PET/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS).

INTRODUCTION: Primary aldosteronism (PA) is the most common form of secondary hypertension. It is caused by overproduction of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction is crucial, because PA is cured by adrenalectomy in APA and is treated by mineralocorticoid receptor antagonists in BAH. The distinction is currently made by adrenal vein sampling (AVS). AVS is a costly, invasive and complex technical procedure with limited availability and is not superior in terms of outcomes to CT scan-based diagnosis. Thus, there is a need for a cheaper, non-invasive and readily available diagnostic tool in PA. We propose a new diagnostic imaging modality employing the positron emission tomography (PET) tracer [68Ga]Ga-PentixaFor. This tracer has high focal uptake in APAs, whereas low uptake was shown in patients with normal adrenals. Thus, [68Ga]Ga-PentixaFor PET/CT is an imaging modality with the potential to improve subtyping of PA. It is readily available, safe and, as an out-patient procedure, much cheaper diagnostic method than AVS. METHODS AND ANALYSIS: We present a two-step randomised controlled trial (RCT) protocol in which we assess the accuracy of [68Ga]Ga-PentixaFor PET/CT in the first step and compare [68Ga]Ga-PentixaFor PET/CT to AVS in the second step. In the first step, the concordance will be determined between [68Ga]Ga-PentixaFor PET/CT and AVS and a concordance probability is calculated with a Bayesian prediction model. In the second step, we will compare [68Ga]Ga-PentixaFor PET/CT and AVS for clinical outcome and intensity of hypertensive drug use defined as daily defined doses in a RCT. ETHICS AND DISSEMINATION: Ethics approval was acquired from the medical ethical committee East-Netherlands (METC Oost-Nederland). Results will be disseminated through peer-reviewed articles. TRIAL REGISTRATION NUMBER: NL9625.

Direct Comparison of Real-world Effectiveness of Biologics for Psoriasis using Absolute and Relative Psoriasis Area and Severity Index Scores in a Prospective Multicentre Cohort.

Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-α)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study.

Trends and projections in the incidence of oesophageal cancer in the Netherlands: An age-period-cohort analysis from 1989 to 2041.

In Western populations, the incidence of oesophageal squamous cell carcinoma (OSCC) has been declining, whereas the incidence of oesophageal adenocarcinoma (OAC) has been increasing. Our study examines temporal trends in the incidence of oesophageal cancer in the Netherlands between 1989 and 2016, in addition to predicting future trends through 2041. Data from the Netherlands Cancer Registry and Statistics Netherlands were collected to obtain incidence trends of OSCC and OAC for the period 1989 to 2016. Age-period-cohort (APC) modelling was used to estimate the contribution of age, calendar period and birth cohort on the observed incidence trends. To predict the future numbers of new cases of both OSCC and OAC from 2017 to 2041, log-linear APC models were fitted to the trends of 1989 to 2016. The age-standardised incidence rates of OSCC have decreased slightly for men and increased slightly for women. In contrast, a marked increase in the incidence of OAC was observed, ranging from 2.8 per 100 000 persons in 1989 to 10.1 in 2016. This increase in OAC incidence was more prominent in men, and it will result in an increased risk of OAC for successive generations. Future projections indicate that the incidence of OAC will further increase to 13.1 per 100 000 persons in 2037 to 2041, meaning that there will be 13 259 cases of OAC in 2037 to 2041, as compared to 9386 diagnoses in 2017 to 2021. The changing epidemiologic trends in oesophageal cancer in the Netherlands should be reflected in the development of prevention, early detection and treatment strategies.

Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER): Protocol for a Longitudinal Observational Study.

BACKGROUND: One in three patients with psoriasis will develop psoriatic arthritis (PsA). If left untreated, this can lead to pain, impaired function, and irreversible joint damage. Timely recognition and referral to a rheumatologist are therefore key. However, current methods used to screen patients with psoriasis for those who might benefit from referral to a rheumatologist are not performing well enough. OBJECTIVE: The Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER) study is designed to determine the prevalence of PsA in a psoriasis population and to find parameters that can be used to develop a new or enhance an existing instrument for a rheumatological referral. METHODS: DAPPER is a longitudinal observational study with a 1-year follow-up. Patients with psoriasis (N=300) who are treated at an outpatient dermatological clinic will be screened extensively for signs and symptoms of PsA by a trained rheumatologist. If there is clinical suspicion of PsA and the patient is not yet treated by a rheumatologist, referral to the Department of Rheumatology will follow for confirmation of the diagnosis and further care. After 1 year, data on changes in quality of life and PsA and psoriasis disease activity will be collected from the referred patients. The screening visit will be used to gather demographical and medical data, which can later be used to develop the aforementioned screening instrument. RESULTS: Inclusion started in June 2019 and finished in June 2021. Follow-up with newly discovered patients with PsA is ongoing. CONCLUSIONS: The DAPPER study is specifically designed to improve the detection of existing PsA in a dermatologic outpatient setting. Although internal validity will be tested, external validity will have to be checked using a second validation cohort. To predict the development of PsA in the future, longitudinal/prospective data collection is required and will be performed in a follow-up study (DAPPER-i). TRIAL REGISTRATION: Dutch Trial Register NTR7604; https://www.trialregister.nl/trial/7397. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31647.

The Additional Effect of Individualized Prescriber-Focused Feedback on General Guideline Instruction in Reducing Antipsychotic Polypharmacy in Inpatients.

PURPOSE/BACKGROUND: Antipsychotic polypharmacy (APP) is the concurrent use of more than one antipsychotic by a patient. Multiple antipsychotics are often prescribed, although all relevant guidelines discourage this practice. These recommendations are based on a lack of evidence for effectiveness and an increased risk of serious adverse events with APP. Studies on the effects of educational interventions targeted at physicians have demonstrated inconclusive results. Moreover, it is unclear how individualized these interventions need to be. In this study, we aimed to assess the effect of a general intervention and the additional impact of an individualized, prescriber-focused intervention on guidelines adherence, that is, the prescription of APP. METHODS/PROCEDURES: We conducted a 36-month 2-step serial intervention study with 4 stages of 9 months each (baseline, general intervention, addition of an individualized intervention, and follow-up) including all 20 inpatient units of one regional mental health organization. The primary outcome was the proportion of patients with regular prescriptions for APP ≥30 consecutive days across all patients with a prescription of at least one antipsychotic. The secondary outcome was the proportion of patient days on APP over the total number of patient days on at least one antipsychotic. FINDINGS/RESULTS: The general intervention was ineffective on both outcome measures. Addition of an individualized intervention decreased the proportion of patients with prescriptions for episodes of persistent APP significantly by 49.6%. The proportion of patient days on APP significantly decreased by 35.4%. IMPLICATIONS/CONCLUSIONS: In contrast to a general intervention, the addition of an individualized intervention was effective in improving adherence to guidelines with respect to APP prescription in inpatients.

Trends and projections in cutaneous melanoma death in the Netherlands from 1950 to 2045.

ABSTRACT: Child sun protection has recently been linked to the future disappearance of fatal melanoma in adults in successive generations. In the Netherlands, however, mortality rates from melanoma have increased gradually from the 1950s, with some indication of stabilisation since 2010, which may be compatible with a birth cohort effect by sun-protective measures and screening. To study the trajectories ahead a trend analysis was applied. Numbers of people with cutaneous melanoma as underlying cause of death from 1950 to 2018 and population data were derived from Statistics Netherlands. A graphical approach was used to explore trends in mortality by age, calendar period, and cohorts born in the successive periods of 1889 to 1979. Age-period-cohort modelling outcomes and population forecasts provided projections of mortality until 2045. Based on 24,151 cases of melanoma death (13,256 men, 10,895 women), age-standardised mortality rates were similar from 1950 to 1989 for both genders, and increased thereafter more in men. The age-curve patterns changed gradually towards higher death rates at older age, implying the existence of a birth cohort effect. The age-period-cohort models showed an increase in melanoma mortality rates in successive generations. For women, the birth cohort effect plateaued for generations born since the mid-1980s. The projected total mortality number was predicted to rise in the next 3 decades.It is concluded that a small future decline of mortality in younger generations can be expected in the Netherlands, but mortality is still rising for the total population.

The Skin May Clear But the Arthritis Won't Disappear: Focusing on Concomitant and New-Onset Psoriatic Arthritis in a Daily Practice Cohort of Psoriasis Patients on Biologic Therapy.

BACKGROUND: Previously identified risk factors for psoriatic arthritis (PsA); nail dystrophy and scalp lesions are highly prevalent in patients with moderate-to-severe psoriasis. Therefore, these variables may not be useful as predictors for PsA in this population. OBJECTIVE: We assessed the predictive value of demographic and clinical characteristics for development of PsA in a cohort of patients with moderate-to-severe psoriasis, currently treated with biologics. Furthermore, we reported the incidence of new-onset PsA in this population and described the characteristics of patients that developed PsA during biologic treatment. METHODS: Demographics and treatment characteristics of psoriasis patients currently using biologic therapy were extracted from the BioCAPTURE database (n=427). Poisson regression was used to calculate incidence rates. Multivariable logistic regression was performed to identify factors independently associated with PsA onset. Patient and treatment characteristics of patients that developed PsA during biologic treatment were described. RESULTS: The incidence of PsA was 1.0 (95% CI 0.8-1.2) per 100 psoriasis-years. Except for a lower risk for PsA in male gender (OR 0.58, 95% CI 0.34-0.98, p-value 0.04), no clinical factors were significantly associated with an altered risk of developing PsA. During biologic therapy, 32 patients (9.4%) newly developed PsA. In this group, 53.8% had PASI<5 at PsA diagnosis. The incidence rate of PsA was 1.6 (95% CI 1.1-2.2) per 100 years on biologic therapy. CONCLUSION: Clinical risk factors might be inaccurate to predict PsA onset in patients with moderate-to-severe psoriasis on biologics. Even with low disease activity, psoriasis patients on biologics are still prone to develop PsA.

Reduced neurobehavioral functioning in agricultural workers and rural inhabitants exposed to pesticides in northern Chile and its association with blood biomarkers inhibition.

BACKGROUND: Previous biomonitoring studies have shown that people in the rural population of Coquimbo, the major agricultural area in northern Chile are being occupationally and environmentally exposed to organophosphate/carbamate (OP/CB) pesticides. Given their harmful effects, this study had two aims; first, to evaluate the effect of cumulative or chronic exposure to OP/CB pesticides on the neurobehavioral performance of agricultural workers and rural inhabitants; second, to determine if changes in the neurobehavioral performance are associated to changes in blood biomarkers of OP/CB pesticides during the spray season, when exposure is higher. METHODS: For the first aim, a cross sectional study of neurobehavioral performance in adult volunteers (men and women, 18-50 years-old, right-handed) was carried out in the pre-spray season. Sampling was done by convenience and a questionnaire was used to categorize participants depending on their level of chronic exposure, as either: occupationally exposed (OE, n = 87), environmentally exposed (EE, n = 81), or non-exposed controls or reference group (RG, n = 100). A neurobehavioral test battery consisting of 21 tests to measure cognitive, motor and emotional state was applied. For the second aim, neurobehavioral measures were taken a second time from EE and OE groups during the spray season, and their exposure corroborated by blood-based biomarker inhibition. RESULTS: Lower neurobehavioral performance was observed in the pre-spray evaluation of EE and OE groups compared to the non-exposed, OE being the worst performing group. Seasonal exposure impaired performance in both exposure groups on all tests except those on attention and mood. Data modeling of the basal (pre-spray) measurements showed that the level of exposure was the best predictor of performance. During spraying, inhibition of BChE activity in the EE group was the best predictor of low performance in tests measuring logical, auditory and visual memory, inhibitory control of cognitive interference, constructional and planning abilities, executive functions, and motor speed and coordination. CONCLUSION: Long-term occupational or environmental exposure to pesticides caused impairment in neurobehavioral functioning, which worsened during the spraying season, mainly in EE. BChE inhibition was the best predictor for seasonal neurobehavioral changes in EE.

Association between cholinesterase's inhibition and cognitive impairment: A basis for prevention policies of environmental pollution by organophosphate and carbamate pesticides in Chile.

BACKGROUND: In Chile organophosphate pesticides are widely used in the production of fruits. Pesticides use is regulated for professional practice but there is no regulation regarding exposure to the general population. OBJECTIVE: To relate exposure to cholinesterase's inhibitor pesticides during the spray season with neuropsychological impairment in occupationally exposed (OE) and environmentally exposed (EE) groups of people. METHODS: Exposure was assessed through inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity and neuropsychological outcomes were evaluated through a large battery of tests covering general mental status, language, memory, attention, executive function, praxis and psychomotricity. Evaluations were carried out firstly in a period of no/low organophosphate pesticide use and subsequently during the spray season. All parameters were calculated as the relative change from baseline to spray season. RESULTS: For this study in total 156 participants were recruited divided equally over participants with environmental exposures (EE) and participants with occupational exposure (OE). In the EE, BChE's enzyme activity inhibition ≥30% showed significant association with 10% or more decreased performance in several tests evaluating six of the eight cognitive areas (excepting psychomotricity and mood status); besides, for AChE inhibition in EE, the association was significant in three tests evaluating attention and one of executive function. Whereas, in OE, the inhibition of the BChE ≥30% was associated with a low performance of one attention test and for AChE the exceedance of the standard was associated with diminished performance in one test of memory and attention, respectively. The association between biomarkers of biological effect and cognitive impairment persisted among the EE group after removing confounders. No association was found between biomarkers of biological acute effect and decreased cognitive performance in the OE group. CONCLUSIONS: Increased exposure to pesticides was confirmed by increased inhibition of cholinesterase's in both exposure groups; which was associated with a diminished neuropsychological performance, mainly in the environmentally exposed study group. [310 words].

Patients' and gynecologists' views on sentinel lymph node mapping in low- and intermediate-risk endometrial cancer: a Dutch vignette study.

OBJECTIVE: Sentinel lymph node (SLN) mapping in endometrial cancer is gaining ground. However, patient views on this new technique are unknown. The aim of this study was to determine factors important to patients and gynecologists when considering SLN mapping in low- and intermediate-risk endometrial cancer. METHODS: We performed a vignette study. Patients who underwent a total hysterectomy for low- or intermediate-risk endometrial cancer between 2012 and 2015 were invited. Dutch gynecologists specializing in gynecologic oncology were also invited. We based the selection for attributes in the vignettes on literature and interviews: risk of complications of SLN mapping; chance of finding a metastasis; survival gain; risk of complications after radiotherapy; operation time; and hospital of surgery (travel time). We developed a questionnaire with 18 hypothetical scenarios. Each attribute level varied and for each scenario, participants were asked how strongly they would prefer SLN on a scale from 1 to 7. The strength of preference for each scenario was analyzed using linear mixed effects models. RESULTS: A total of 38% of patients (41/108) and 33% of gynecologists (42/126) participated in the study. Overall, they had a preference for SLN. The mean preference for patients was 4.29 (95% CI 3.72 to 4.85) and 4.39 (95% CI 3.99 to 4.78) for gynecologists. Patients' preferences increased from 3.4 in the case of no survival gain to 4.9 in the case of 3-year survival gain (P<0.05) and it decreased when travel time increased to >60 min (-0.4, P=0.024), or with an increased risk of complications after adjuvant radiotherapy (-0.6, P=0.002). For gynecologists all attributes except travel time were important. CONCLUSIONS: Overall, patients and gynecologists were in favor of SLN mapping in low- and intermediate-risk endometrial cancer. Most important to patients were survival gain, travel time, and complication risk after adjuvant radiotherapy. These preferences should be taken into account when counseling about SLN mapping.

Adrenal venous sampling: cosyntropin stimulation or not?

Notwithstanding the high prevalence of primary aldosteronism (PA), probably the most common form of secondary hypertension, the diagnosis of PA is often neglected or delayed, thus precluding target treatment, which is curative in many cases. For selection of the most appropriate treatment, a fundamental step is the distinction between a lateralized form, mainly aldosterone-producing adenoma (APA), and bilateral adrenocortical hyperplasia (BAH), also known as idiopathic hyperaldosteronism (IHA). To this aim all current guidelines recommend adrenal vein sampling (AVS), a technically challenging procedure that often fails, particularly in non-experienced hands. Cosyntropin (synthetic ACTH) is administered in the attempt to maximize adrenal cortisol secretion and avoid pulsatile adrenocortical hormone secretion in about 40% of the referral centres around the world. However, the Endocrine Society guidelines do not advise about the use or not of cosyntropin as stimulus during AVS, as there are arguments in favour and against its use. These arguments are presented in this debate article reflecting the views of groups that currently use and do not use cosyntropin.

Ethanol sclerotherapy or polidocanol sclerotherapy for symptomatic hepatic cysts.

BACKGROUND: Over the past decades, multiple approaches to aspiration sclerotherapy of large symptomatic hepatic cysts have been investigated. However, comparative data are scarce. OBJECTIVE: The objective of this article is to compare cyst reduction, symptomatic relief, and adverse events between ethanol sclerotherapy and polidocanol sclerotherapy. METHODS: This retrospective study included adults having a symptomatic hepatic cyst treated at a European tertiary referral center with ethanol sclerotherapy (Center 1) or polidocanol-sclerotherapy (Center 2). We compared cyst diameter reduction (%) and symptom improvement (yes/no) within 12 months' post-treatment between centers using multivariate regression analyses adjusted for confounding factors. Finally, we compared adverse events using Fisher's exact test. RESULTS: We included 71 patients from Center 1 and 66 patients from Center 2 (median age 57 years; 126/137 (92%) female). Cyst reduction was comparable between Centers 1 and 2: 37.5% (IQR 15.7-61.0%) versus 44.2% (IQR 24.6-60.5%), respectively (p = 0.35). Correspondingly, symptomatic relief was comparable: 30/53 (56.6%) versus 43/66 (65.2%), respectively (p = 0.88). Center 1 reported significantly more (11 versus 3; p = 0.047) adverse events than Center 2. CONCLUSION: We found comparable cyst reduction and symptomatic relief rates between ethanol- and polidocanol sclerotherapy, while adverse events occurred more often in the ethanol group. Prospective studies focused on clinical response are needed to further explore differences between approaches.

Substantial clinical benefit for Neck Disability Index revisited: establishing the goal for treatment?

PURPOSE: It is difficult for clinicians to inform patients about the success rate of a treatment as a cervical anterior discectomy procedure. Ideally, a proportion of good outcome as rated by patients is known. Patient-reported outcome measurements are helpful. The purpose is to relate the difference in Neck Disability Index (NDI) after a cervical anterior discectomy procedure for single level cervical degenerative disc disease with the patients' rating of their actual clinical situation after long-term follow-up to define the substantial clinical benefit (SCB). METHODS: After completion of the NDI, patients who were surgically treated for cervical single level degenerative disease were asked to complete a five-item Likert scale to rate their clinical situation. After dichotomisation of the outcome in good versus less than good, a cut-off value was defined by determining the value of the difference of NDI with the highest specificity and sensitivity. Funding was not obtained. RESULTS: SCB for NDI after surgery for cervical single level degenerative disease should be set at ten with area under the curve (AUC) of 0.71 for sensitivity as well specificity. CONCLUSIONS: The goal for each treatment is a good outcome. While comparing treatments for cervical degenerative disc disease only those with an SCB of ten will be relevant for the patient, as patients who achieved this difference in NDI rated their actual situation at long-term follow-up as good.

Quality of Life in Primary Aldosteronism: A Comparative Effectiveness Study of Adrenalectomy and Medical Treatment.

Context: In primary aldosteronism (PA), two subtypes are distinguished: aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). In general, these are treated by adrenalectomy (ADX) and mineralocorticoid receptor antagonists (MRA), respectively. Objective: To compare the effects of surgical treatment and medical treatment on quality of life (QoL). Design: Post hoc comparative effectiveness study within the Subtyping Primary Aldosteronism: A Randomized Trial Comparing Adrenal Vein Sampling and Computed Tomography Scan (SPARTACUS) trial. Setting: Twelve Dutch hospitals and one Polish hospital. Participants: Patients with PA (n = 184). Interventions: ADX or MRAs. Main Outcome Measures: At baseline and 6-month and 1-year follow-up, we assessed QoL by two validated questionnaires: RAND 36-Item Health Survey 1.0 (RAND SF-36) and European Quality of Life-5 Dimensions (EQ-5D). Results: At baseline, seven of eight RAND SF-36 subscales and both summary scores, as well as three of five EQ-5D dimensions and the visual analog scale, were lower in patients with PA compared with the general population, especially in women. The beneficial effects of ADX were larger than for MRAs for seven RAND SF-36 subscales, both summary scores, and health change. For the EQ-5D, we detected a difference in favor of ADX in two dimensions and the visual analog scale. Most differences in QoL between both treatments exceeded the minimally clinically important difference. After 1 year, almost all QoL measures had normalized for adrenalectomized patients. For patients on medical treatment, most QoL measures had improved but not all to the level of the general population. Conclusion: Both treatments improve QoL in PA, underscoring the importance of identifying these patients. QoL improved more after ADX for suspected APA than after initiation of medical treatment for suspected BAH.

What's the best surgical treatment for patients with cervical radiculopathy due to single-level degenerative disease? A randomized controlled trial.

BACKGROUND: To investigate the efficacy of adding supplemental fusion or arthroplasty after cervical anterior discectomy for symptomatic mono-level cervical degenerative disease (radiculopathy), which has not been substantiated in controlled trials until now. METHODS: A randomized controlled trial is reported with 9 years follow up comparing anterior cervical anterior discectomy without fusion, with fusion by cage standalone, or with disc prosthesis. Patients suffering from symptomatic cervical disk degeneration at one level referred to spinal sections of department of neurosurgery or orthopedic surgery of a large general hospital with educational facilities were eligible. Neck Disability Index (NDI), McGill Pain Questionnaire Dutch language version (MPQ-DLV), physical-component summary (PCS), and mental-component summary (MCS) of the 36-item Short-Form Health Survey (SF-36), and re operation rate were evaluated. FINDINGS: 142 patients between 18 and 55 years were allocated. The median follow-up was 8.9±1.9 years (5.6 to 12.2 years). The response rate at last follow-up was 98.5%. NDI at the last follow-up did not differ between the three treatment groups, nor did the secondary outcomes as MPQ-DLV and PCS or MCS from SF-36. The major improvement occurred within the first 6 weeks after surgery. Afterward, it remained stable. Eleven patients underwent surgery for recurrent symptoms and signs due to nerve root compression at the index or adjacent level. CONCLUSIONS: This randomized trial could not detect a difference between three surgical modalities for treating a single-level degenerative disk disease. Anterior cervical discectomy without implant seems to be similar to anterior cervical discectomy with fusion by cage stand-alone or with disk prosthesis. Due to the small study sample size, this statement should be considered as inconclusive so far. TRIAL REGISTRATION: ISRCTN41681847.

The Qualification of Outcome after Cervical Spine Surgery by Patients Compared to the Neck Disability Index.

OBJECTIVE: The Neck Disability Index (NDI) is a patient self-assessed outcome measurement tool to assess disability, and that is frequently used to evaluate the effects of the treatment of neck-related problems. In individualized medicine it is mandatory that patients can interpret data in order to choose a treatment. A change of NDI or an absolute NDI is generally meaningless to a patient. Therefore, a correlation between the qualification of the clinical situation rated by the patient and the NDI score was evaluated. METHODS: Patients who completed an NDI after anterior surgery because of symptomatic single level degenerative cervical disc disease were asked one month after completion of the NDI to qualify their clinical situation of a 5-item Likert scale varying from excellent to bad. Since a clear distinction between the categories was not possible based on the total NDI score, a ROC-curve was built, and the AUC computed in order to estimate best dichotomization in qualification of the clinical situation. The best corresponding cut-off point for the NDI total score was found by studying sensitivity and specificity for all possible cut-off points. RESULTS: 102 patients were included. The highest AUC was obtained by dichotomizing the qualification into a group with good outcome and less-good outcome. The highest sensitivity and specificity for the dichotomized qualification as good outcome corresponded to a NDI ≤ 7. Sensitivity was 81.08% and specificity was 78.57%. CONCLUSION: This is the first study that correlated the qualification of the situation by the patients themselves and NDI. An NDI ≤ 7 corresponded to a good outcome according to the patients. This is valuable information to inform patients in their decision for any treatment.

Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial.

BACKGROUND: The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism. METHODS: In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654. FINDINGS: We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3·0 [IQR 1·0-5·0] vs 3·0 [1·1-5·9], p=0·52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0·87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0·82). On secondary endpoints we found no differences in health-related quality of life (median RAND-36 physical scores 52·7 [IQR 43·9-56·8] vs 53·2 [44·0-56·8], p=0·83; RAND-36 mental scores 49·8 [43·1-54·6] vs 52·7 [44·9-55·5], p=0·17) for CT-based and AVS-based treatment. Biochemically, 37 (80%) of patients with CT-based adrenalectomy and 41 (89%) of those with AVS-based adrenalectomy had resolved hyperaldosteronism (p=0·25). A non-significant mean difference of 0·05 (95% CI -0·04 to 0·13) in quality-adjusted life-years (QALYs) was found to the advantage of the AVS group, associated with a significant increase in mean health-care costs of €2285 per patient (95% CI 1323-3248). At a willingness-to-pay value of €30 000 per QALY, the probability that AVS compared with CT constitutes an efficient use of health-care resources in the diagnostic work-up of patients with primary aldosteronism is less than 0·2. There was no difference in adverse events between groups (159 events of which nine were serious vs 187 events of which 12 were serious) for CT-based and AVS-based treatment. INTERPRETATION: Treatment of primary aldosteronism based on CT or AVS did not show significant differences in intensity of antihypertensive medication or clinical benefits for patients after 1 year of follow-up. This finding challenges the current recommendation to perform AVS in all patients with primary aldosteronism. FUNDING: Netherlands Organisation for Health Research and Development-Medical Sciences, Institute of Cardiology, Warsaw.